Friday, April 30, 2010

Suffering is part of the deal. 1 Peter 4:12-19

It's a shock to find you have a terminal illness. It's a shock when your father dies. It's a shock when a friend is lost in an air crash. It's a shock when you lose a child.

These are certainly shocking things, but they are not surprising. Everyone has to die. Bad things happen.

Unfortunately, some Christians make a shipwreck of their faith because bad things surprise them. In the Old Testament the rule was obey and you will be blessed; disobey and you will be cursed. If you read the books of Kings or Chronicles you can see this acted out. Good kings are blessed; bad kings are cursed.

But even in the Old Testament this is not a universal rule. Job, a good man, was cursed, not his whingeing companions. Joseph was sold into slavery, not his spiteful brothers. And look at David's suffering; a man after God's own heart. Consider Jeremiah or Elijah. They spoke God's word and they suffered for it.

The point is that the Old Testament is about Jesus. It is he who deserves blessing for his righteousness; yet it is he who volunteers for the suffering that is due to the unrighteous. Isaiah chapter 53 tells us this quite clearly

In the New Testament it is quite plain that suffering is part of the deal. There is glory to come, but suffering first. Anyone who expects plain sailing into the sunset hasn't read their New Testament.

In today's passage 1 Peter 4:12-19 we are told not to be surprised.

Dear friends, do not be surprised at the painful trial you are suffering, as though something strange were happening to you. But rejoice that you participate in the sufferings of Christ, so that you may be overjoyed when his glory is revealed. If you are insulted because of the name of Christ, you are blessed, for the Spirit of glory and of God rests on you. If you suffer, it should not be as a murderer or thief or any other kind of criminal, or even as a meddler. However, if you suffer as a Christian, do not be ashamed, but praise God that you bear that name. For it is time for judgment to begin with the family of God; and if it begins with us, what will the outcome be for those who do not obey the gospel of God? And, "If it is hard for the righteous to be saved, what will become of the ungodly and the sinner?" So then, those who suffer according to God's will should commit themselves to their faithful Creator and continue to do good.

Previous generations of Christians didn't need telling about this simple truth. There will be glory, but suffering is part of the deal. Romans 8:17 - Now if we are children (of God), then we are heirs - heirs of God and co-heirs of Christ, if indeed we share in his sufferings in order that we may also share in his Glory. There is nothing strange about it.

The NIV translates this passage poorly. It's not a painful trial, but a fiery trial and it's a trial 'to test you'. The KJV has the fiery trial which is to try you, the NASB fiery ordeal among you, which comes upon you for your testing and the ESV the fiery trial when it comes upon you to test you.

We sing about "Refiner's fire" and such it is. "Our dross to consume" says the old hymn. How we react to the suffering is crucial. Fair-weather Christians who have been poorly taught, may crumple when hardship comes, but consider the Cuban Christians slaughtered by Castro. They went to their deaths singing, "Christ is the Victor!" and "Jesus reigns!" so that the guards had to gag them in an attempt to stop people who heard them from being converted.

Do you seek assurance? Do you want to know that there is glory to come? Then rejoice in present suffering and you will be overjoyed when Jesus comes or calls. Paul talks about 'sharing in the fellowship of his sufferings' (Philippians 3:10) To Paul it is a guarantee of the resurrection to come. Technically the Greek here links the power of the resurrection and the fellowship of sharing in his sufferings as a single entity, with a single definite article. You can't have one without the other.

Many have testified to being especially blessed when suffering particularly as a Christian. We will all suffer because of the curse that is upon the world consequent on the Fall, but putting yourself on the line - in testimony or witness - implies a special blessing. We are easily cowed from witnessing by the fear of what men might think of us. The world can be a callous place. Mockers jeer at you if you wear your faith on your sleeve. Remember how Tony Blair's spokesman said for him, "We don't do God." I have sometimes held back from speaking to smart people for fear of being thought of as a God-botherer or some such insulting phrase - preferring the respect of my colleagues to the approval of my God. but on other occasions I have been forthright for the gospel and scorned their shame. On such occasions there is a special blessing. You feel exhilarated and true to yourself.

What Peter promises is that the "Spirit of glory and of God" will rest upon you. "Be bold! Be strong!" says the children's song. "If you suffer as a Christian, do not be ashamed!" says Peter, "But praise God that you bear that name." Since I was diagnosed with cancer I have been much bolder. Perhaps because my journey's end is closer. Perhaps because I have nothing else to lose.

The Devil's current strategy, at least in England, is to try and make people ashamed of being called a Christian. Perhaps it is so in other lands? Alternative comedians mock the faith, judges dismiss it, politicians ignore it and intellectuals tell mendacious lies about it.

What do they know? What need have we for the world's applause. These people lead hollow lives, without purpose or meaning. Rather seek the Lord's approval, "Well done, thou good and faithful servant!" The Devil was ever the father of lies.

Are you afraid of judgement? Only those who are in the wrong need do so. When a soccer player is the victim of a foul, he will often leap up and mime the showing of a red card to the perpetrator. He seeks judgement. However if it were the one who committed the foul he will slink away into a melee of players, hoping to escape justice. There are many who have banked on this life being all there is, who hope to escape justice. What folly! The fool says in his heart there is no God. In a sense we all get out of this life alive, but then we have to face the judgement. Then you won't be able to cover your sins by hiding in a melee of players. They could be covered, though, for Jesus' blood never failed us yet. For those who are covered by his blood - will be seen a Jesus by the Judge of all the earth, who will surely do right.

Finally, be committed. Your Creator is faithful to you; will you not be faithful to him? You should not give up as you approach the tape. You have run the Marathon. You are scarred by the journey. You are battered and bruised. But do not give up. Last week in the London Marathon, the elite runners made it easily in near record time. But there were thousands who struggled to do it in 5 hours or more. There was one man, injured in Afghanistan, kept going by electronic implants in his muscles. He was going to take all day to do the journey, but he was going to finish. He knew that many charities depended on his finishing to raise their funds. He would not give up.

Peter tells us to continue to do good. Yet not Peter, but the Spirit of Jesus. If it were I that was telling you, you might ask who I was to dictate to you. My suffering might well have been minor compared to yours and you might think I have a colossal cheek. But Jesus suffered far beyond anyone else. He took the whole weight of your sin and mine on his shoulders. Such was the trauma that the whole godhead was wrenched apart. He literally went through hell for us.

He's telling us. Continue to be good.

Small government is the answer

Gary McFarlane is a black, Pentecostal, marriage guidance counsellor. He was dismissed from his job working for the Marriage Guidance Council. The grounds for his dismissal was that he was asked whether in a hypothetical situation he would be willing to give advice on sexual techniques to a homosexual couple. He told his employers that he would be unable to do so, since his religious views made this an affront to his conscience.

I should say that the MGC has changed its name to the more trendy "Relate", so he was unable to use the excuse that a homosexual couple would not have been married. Relate receives most of its funds from a government (read taxpayer) grant.

I would have answered the question in the positive I would have given the couple the same advice that Bob Newhart gave in the famous comedy sketch where he played a psychiatrist. He only charged $5 for his advice since the sessions never lasted more than 5 minutes, the advice consisted of two words and was the same for all manner of psychiatric illness whether it was compulsive hand washing, claustrophobia or anorexia nervosa. The advice, shouted at the patient, was, "Stop it!"

Of course, I am joking. (Please don't write in and complain that I am making light of a serious situation. I know. I just wanted to amuse my readers.)

Mr Justice Laws has decreed that Mr McFarlane may not appeal against the decision that he was not unfairly dismissed since there could be no special dispensation in English law for the Christian religion (even though English law derives from Christian principles).

This is in an interesting break with the past. When abortion became legal, special provision was made to exempt doctors from being involved in abortions if their conscience was against it. When Sunday trading was brought in, shop employees who objected to working on Sundays were exempt for its provision. However, when the government decided that adoption agencies must be willing to place children with gay couples, Catholic adoption agencies were forced either to separate themselves from the Catholic church or not accept the government's (ie taxpayer's) money.

I think this is the nub of the problem. The State should not be involved in such things. Individual taxpayers are not asked whether they want their money spent on gay adoptions of sexual advice for gay couples. Almost certainly they would say no if asked. However, governments are elected for 5 years and can do what they want once elected. We do not have democracy but an elected dictatorship. At least we can throw them out after five years. Many charitable organizations have their origing in Christian organizations, but in taking government money they have been forced to accept secular standards. The remedy is to set up parallel organization for Christians and avoid like the plague anything with HMG stamped upon it. We also need to vote in a party committed to small government.

Thursday, April 29, 2010


Gordon Brown has almost certainly blown his chances (slim though they were) in the general election in what has already been called 'Bigotgate'.

The facts are simple. He was out meeting the people in the marginal constituency of Rochdale. He got into a conversation with a senior lady who has been a long-term Labor supporter. She questioned him about taxation, benefits, education and immigration.

Of course, he didn't answer her questions but parroted responses from the Peter Mandelson phrase book reacting to key words with an instinctive motif. When he got back to his car he complained that he had been set up with her and blamed one of his female aides. He then called the old woman a bigot.

What he didn't remember was that at his own party's request he had been miked up for the encounter and the mike was still switched on.

Later, he was confronted on air with his remarks. He blustered. Then he altered his itinerary to call at the woman's house to make a grovelling apology.

The whole episode has demonstrated how out of touch he is with ordinary voters. If the woman was bigoted then so are three-quarters of the population. It showed him to be a bully, picking on a female aide. Journalists have been telling us this for weeks, but not everybody has been convinced. It showed him to be maladroit, to have poor judgement in going back to apologise (the damage was done and any apology would sound insincere) and to lack the sure-footedness that a prime minister needs.

Gordon Brown was never elected prime minister; he inherited the job from Tony Blair. It is plain to see why Blair led the party at his expense. Even in 1997 had he been leader, Labour would never have been elected.

Monday, April 26, 2010

Pope insulted

The Pope is due to visit Britain later this year, though that visit has been put in jeopardy by a leaked Foreign Office memo which made the silly suggestions that the Pope might open an abortion clinic, preside over a gay wedding and launch a new brand of 'Benedict' condoms while he was here.

This is the sort of puerile joking that young men are prone to when in their cups. The perpetrator, was probably still drunk when he circulated the 'joke' in an e-mail. Thanks to the Daily Telegraph we now know his name. Steven Mulvain was educated at the £9,279-a-year King’s School, Tynemouth, before studying English at Balliol College, Oxford. He taught at a summer school in northern Germany in 2006, where he said in a podcast that his hobbies included “drinking a lot and reading more or less what I want”.

A spokesman for the Foreign Office said “Many of the ideas in the document are clearly ill-judged, naïve and disrespectful” and the department was “deeply sorry for the offence which it has caused”.

Mulvain has not been dismissed, but moved sideways in a curious reprise of the Catholic Church's response to the exposure of pedophile priests.

I happen to agree with the pope over abortion and gay marriage, though I believe that Roman Catholicism has it wrong on contraception and unmarried priests. I suspect that the pedophile problem is at least added to by the fact that RC priests don't marry, though this is more an indirect than a direct consequence. I suspect that the priesthood provides a sanctuary for those with pedophile tendency partly because those who are married are not competing for the posts, partly because of the availability of choirboys, partly because the Catholic Church is held in such high esteem in some places that parishioners will hear no word against it and partly because of the forgiving attitude of a church that believes in redemption. It has to be said that Islam has its own problems with pederasty, and most child abuse occurs within the family.

Nonetheless, the cover-up was unforgivable.

Thursday, April 22, 2010

Christ's attitude: Prayer and Love. 1 Peter 4:7-11

Sebastian Vettel has had more pole positions than anyone else this Formula 1 season, but he has flattered to deceive. His Red Bull car has not lasted the pace. Many people start well, but it is finishing that matters. Perseverance is all.

How many marriages are fine for the first few years, but crumble when the going gets tough? They say that all political careers end in failure, but that is probably because politicians get to thinking that they are invincible. The great message of the Bible is that you can't do it by yourself. The great temptation of the Devil is to make you think you can.

It is a particular temptation for the bright and talented. Success comes easily to them and they grow too big for their boots. If you read the gospels, you can't help but be attracted to Jesus. Such wit; such wisdom; such self effacement! How can you help wanting to be like him? So you set out to do so, but very soon you fall short. You easily forgive yourself and make allowance for circumstances. You try harder but still you fail. What do you do when you recognize that you are not up to the mark? Do you think the mark is not worth getting up to? Do you put it down to an unrealistic childish ambition? Do you reconcile yourself to failure and seek other means of fulfillment?

It never ceases to amaze me how many men and women of great attainment start out from an evangelical background but are diverted into other pathways. Their achievements may be great, but they have given up their previous standards and ambitions. Thomas Hardy was one such; George Eliot another.

This passage in 1 Peter 4: 7-11 tells us how we should rather react.

The end of all things is near. Therefore be clear minded and self-controlled so that you can pray. Above all, love each other deeply, because love covers over a multitude of sins. Offer hospitality to one another without grumbling. Each one should use whatever gift he has received to serve others, faithfully administering God's grace in its various forms. If anyone speaks, he should do it as one speaking the very words of God. If anyone serves, he should do it with the strength God provides, so that in all things God may be praised through Jesus Christ. To him be the glory and the power for ever and ever. Amen.

Life is not a race of a set distance. For some it is a sprint; for some a marathon. We are all a heartbeat away from the end of all things and the Lord is very close. His return is imminent. Like a kingfisher skimming over a lake he might breach the surface at any moment. We should always be ready to meet our God. It's no use putting things off until the times are more opportune.

Peter gives us two instructions on how we are to assume the attitude of Christ. We are to pray and to love.

In order to pray we must be clear minded and self-controlled.

First, our minds must be clear. Praying is not about dashing off a few phrases or performing a ritual. It requires thinking.

Imagine you have a daily audience with the President or the Prime Minister. You wouldn't wing it! You would prepare what you wanted to say beforehand. Your audience with the King of Kings is more important than that! Of course, he knows what you need before you ask, but for his own reasons he has decided only to give you those things when you ask for them.

My son phoned me half an hour ago to tell me that he had safely returned from China. I was delighted to hear him speak. It seems embarrassing, but that is exactly how our heavenly father feels when we speak to him. Why is it such a low priority for us?

Yet we have to admit that it is. Most of us find prayer difficult. It is hard work. And being hard work it requires a clear head. Here is a challenge, for me and for you. Make a fresh start on your prayer time. First find a specific time when you won't be interrupted and make this the first priority of your day. I have been playing house-husband for the past couple of weeks. I know that every day I have to empty the bins and replace the bin-liners. That is a priority, but I mustn't let it become a greater priority than speaking to my heavenly father.

Second, it is useful to adopt a formula for praying and what better than the instruction that Jesus gave us. Many churches say the Lord's prayer as part of their liturgy. I think that is wrong. We don't need to memorise the words and recite them; and certainly not in the KJ version. Don't stumble over trespasses! But to use the Lord's prayer as a template seems to me to be excellent. We should initially concentrate on the centrality of God as the author and finisher of our existence, His holiness and our desire that his will be accomplished, not just at the end times but here and now. We should pray for our own needs, though not for our greeds and especially for our ongoing forgiveness (for we are still sinners) reminding ourselves to forgive those who offend us. We need to pray for protection from the evil one and that we may be able to resist temptation.

We should not forget intercession. I don't know about you, but in my role as a house husband, when I go shopping, I need a list. Everyday I receive dozens of requests for prayer. Unless, I write them down I forget them So keep a notebook or other aide memoire. We should not be shy about making our requests known to God. The Lord's prayer is a guide but not a comprehensive glossary about prayer.

It's not just a clear mind that we need, but also self-control. We are so easily distracted. People used to close their eyes to avoid distraction, but some today find that closing your eyes is a prelude to day-dreaming. Keep them open and consult your notebook. Don't answer the phone - let the answer-phone do it.

Prayer doesn't need to be long-winded with flowery phrases. Make it a conversation as you would talk to your spouse.

The second requirement for the mind of Christ is love. How does love cover a multitude of sins? Like this: suppose my wife says something carelessly that could be wounding if I took it in a certain way - about my expanding middle, for example. Because I love her and she loves me, I don't take offence.

And it's not just my wife who is the recipient of love. Today, a car squeezed me out at a junction. He sounded his horn and made a rude gesture. There was a time when I would have seethed all day. But I let it go. I forgave him, for what it is worth and thought no more about it until now. God so loved me that he gave his one and only son to save me from perishing, why should I not show love to another. In fact showing love is a gift of God - one of the charismata. We have received these grace gifts to serve with, whether speaking, giving hospitality or serving in whatever way we can. These are our love gifts, given to us to pass on to others.

Anemia: the thalassemias.

In many parts of the world in the battle between man and the mosquito, the moggies would have won, were it not for the remarkable way that humans have altered their red blood cells. We have already mentioned sickling and G-6PD deficiency and today I am going to tackle the thalassemias. The thalassemias are a group of condition is which there is a defect in the production of the globin part of hemoglobin.

The body has quite a complicated way of making globin. ordinary hemoglobin is made from two alfa chains and two beta chains. Alfa chains are coded on chromosome 16. There are two alfa genes which are clustered with a gene for the zeta chain, an alfa chain equivalent produced in early embryonic life when blood is made in yolk sac. Both alfa chain genes are active in fetal and adult life and necessary to produce enough alfa chains.

Beta chains are coded on chromosome 11 along with a cluster of beta-like genes, including epsilon, gamma and delta chain genes. Epsilon genes are used by the embryo during yolk sac hemopoiesis. Embryonic hemopoiesis produces Hb Gower 1 and Gower 2 as well as Hb Portland. (Gower 1 is zeta 2, epsilon 2; Gower 2 is alfa 2, epsilon 2; Portland is zeta 2, gamma 2) The fetus uses the gamma chain gene to make HbF (alfa 2, gamma 2) and the adult uses mainly the beta chain gene, with small amounts of delta and gamma chains (HbA is alfa 2, beta 2; HbA2 is alfa 2, delta 2).

This is all very wonderfully designed with the appropriate hemoglobin being made at the different stages of development. For example, baby red blood cells need to snatch oxygen molecules from the mother's blood while the baby is in the womb. It so happens that HbF has a higher affinity for oxygen than HbA, and this is how the baby does it.

For the most part, individuals carrying thalassemia genes suffer no ill effects, but they are protected against malaria. You can usually tell that the individual has it because the red cells are smaller than usual. When we were dealing with iron deficiency we said that a red cell consists mainly of hemoglobin, so the amount of hemoglobin controls the size of the red cell. To little iron means not enough heme and therefore small red cells. In the thalassemias, not enough globin is made and therefore not enough hemoglobin and therefore small red cells result. These individuals are said to have thalassemia trait, meaning that they have inherited a thalassemia gene from only one parent. They are not anemic but they have microcytosis (small red cells).

If you inherit thalassemia genes from both parents then you are probably in real trouble with what is usually a severe illness, but it does depend on whether you inherit the same abnormal gene or a different one. Sometimes inheriting different thalassemia genes can actually make the condition less severe, but the various combinations give a wide variety of conditions from no illness to a fatal one.

There are four clinical states of thalassemia. The most severe is death in the womb. This is called hydrops fetalis - the fetus gets severe heart failure because it isn't making any blood and dies. The second most severe is thalassemia major, in which anemia develops at the age of about 6 months. The body strains to make blood, but hardly succeeds. In the normal adult blood making takes place in the flat bones of the body only - the skull, ribs, sternum, pelvis and spine, but in children it is also made in the bones of the arms and legs. In the fetus it is in addition made in the liver and spleen. In thalassemia major, blood is made in all these places and even in lymph nodes. So, big livers and spleens are the order of the day and the bone marrow so expands that the walls of the bones become very thin. The shape of the face is distorted with prominence of the frontal and maxillary bones, and fractures of the other bones are common.
X-ray of the skull demonstrates the expansion of the medulla and thinning of the cortex and the picture is often referred to a the hair on end appearance. (Picture from

These children have to be treated by blood transfusion. In fact they are heavily transfused to try and suppress the growth of the bone marrow. All this transfusion overloads them with iron which has to be removed or else it gets stuck in various organs, causing staining of the skin, arthritis, and damage to the liver and heart, as well as failure of a host of endocrine organs including the pancreas causing diabetes, the thyroid causing myxedema, the parathyroids causing a low calcium, the testes causing failure of puberty and the pituitary causing small stature.

Removal of iron used to involve nightly subcutaneous infusions of desferrioaxamine which itself was unpleasant and cause cataracts and damage to the retina as well as increasing susceptibility to infections, particularly with salmonella and yersinia. Happily we now have XJade an oral and more efficient chelator.

The least severe form of thalassemia, thalassemia minor, is totally asymptomatic with only a funny blood count to let you know it is there. Between major and minor, there is thalassemia intermedia in which there is anemia and a big spleen, but usually transfusions are not necessary.

Those are the clinical conditions; what are the genetic lesions that cause them?

Hydrops fetalis is caused by a complete absence of alfa chains - they are needed for both HbA and HbF. You have four genes coding for alfa chains, two from each parent. For Hydrops all four have to be missing. If it is recognized early by genetic testing, the baby's life can be saved by intra-uterine transfusion, but the baby will never make its own blood and it will be totally reliant on transfusions unless it could have a stem cell transplant. This sequence of treatments is seldom undertaken and termination of pregnancy is a more likely outcome.

Thalassemia major is usually beta thalassemia major, where a point mutation on both maternal and paternal chromosomes has prevented the production of beta chains. Since you don't need HbA until after birth it does not cause hydrops, but it gradually develops in the first six months of life. Free alfa chains are toxic to the red cell, shortening its survival. Production of other chromosome 16 globin chains, gamma and delta, means that there are increased amounts of HbF and HbA2, which help to soak up the excess alfa chains. If there is a degree of alfa thalassemia, this can lessen the severity of the condition. Rare individuals posess three copies of the alfa chain on chromosome 11 and this makes the condition worse. In some forms of beta thalassemia, small amounts of beta chains are produced which help to ease the condition slightly. Although beta thalassemia major is mainly a sign of two defective beta chains, sometimes the patients are double heterozygotes for beta thalassemia and another hemoglobinopathy.

Thalassemia trait is the non-significant form of thalassemia, only picked up on the blood count.
The blood picture is of a microcytosis with prominent target cells. With beta-thalassemia trait the diagnosis can be confrimed by Hb electrophoresis, though not with alfa thalassemia trait.

Here is is necesary to look for HbH inclusions by incubating the blood with brilliant cresyl blue. If only one alfa gene is missing then the incidence of the 'golf ball' inclusions may be as small as 1 cell in 50,000.though with two genes missing they are a bit commoner.

Thalassemia intermedia may have many causes. The patients are moderately anemic and have large spleens but they don't require regular transfusions. It may be caused by homozygous beta thalassemia - if the gene inherited from both parents allows for the production of some beta chains, or if alfa thalassemia is also inherited, or if a condition called hereditary persistence of fetal hemoglobin (which allows the gamma chains to soak up the excess alfa chains) coexists. Or it might be caused by the asociation of beta thalassemia trait and three (rather than 2) alfa chains on each chromosome 11. Or it could be HbH disease, where three of the four alfa chains have gone missing. Or it could be delta beta thalassemia (where no HbA2 is made). Or it could be Hb Lepore. This is a strange molecule made from the fusion of parts of the beta genes and the delta genes. Homozygotes show intermedia and heterozygotes the trait.

Most forms of alfa thalassemia are caused by deletion of one or more alfa chain gene. Hb Constant Spring is an alfa chain varient in which a mutation affects the termination code so that an elongated chain is produced. this fails to function as a proper alfa chain and effectively produces one of the forms of alfa thalassemia, though these non-deletional forms of alfa thalassemia (and there others with strange names like Hb Quong Sze) tend to be more severe than the deletional forms.

Hemoglobin E is now the commonest form of thalassemia in North America. Newer migrants from South-East Asia have carried the gene. HbE is caused by a substitution of glutamic acid by lysine at codon 26 of the beta chain. This mutation activates a cryptic mRNA splice site which results in reduced synthesis of the mutant beta chain, leading to a thalassemic phenotype. It also interferes with the interface with the alfa chain, leading to increased susceptibility to oxidative stress. Although individuals with homozygous HbE may be similar to Thlassemia trait patients, the condition is variable. Double heterozygotes with HbE and beta thalassemia tend to have thalasemia intermedia with hemolytic crises, though some have a thalassemia major picture. Some patients have benefited from hydroxycarbamide treatment which raises HbF levels.

The thalassemic syndromes are very common throughout the Mediterranean world and in South East Asia. With the migration consequent on war we are seeing and understanding more about these strange conditions.

Wednesday, April 21, 2010

Human breast milk as an anti-cancer agent

One of my correspondents claimed that her CLL improved after she started drinking human breast milk. In today's Telegraph there is a report of a study which seems to confirm that breast milk has anti-cancer properties.

The article suggests that a component of human breast milk, Human Alpha-lactalbumin Made Lethal to Tumour cells or HAMLET, could be a common cancer treatment for adults within five years. Human trials have shown HAMLET can kill bladder cancer and laboratory tests have found it kills 40 different types of cancer, but it is harmless to normal cells. the work is that of Assistant Professor Roger Karlsson, of the University of Gothenburg.

Human trials on male bladder cancers sufferers showed tumours were reduced without side effects within just five days of treatment. However the compound had to be infused into the bladder through a catheter and the professor does not see the compound being infused intravenously or given orally.

Researching this report, I see that it refers to an article in the International Journal of Cancer from 2007, so this may well be old news triggered by a new review.

In fact there is a paper in this month's Journal of Urology which is probably the source of the Telegraph article.

Here is a summary of what it says.

HAMLET is a complex of α-lactalbumin and oleic acid that kills a wide range of tumor cell lines in in vitro conditions. Embryonic cells are intermediately sensitive to HAMLET but healthy differentiated cells tested to date remained viable. The therapeutic potential of HAMLET was established in vivo in patients with skin papilloma. Topically applied HAMLET caused a significant reduction in lesion size. Local infusion of HAMLET into rat brains with invasively growing human glioblastoma xenografts delayed tumor development and prolonged survival. Apoptosis was mainly confined to the tumor area, although HAMLET diffused throughout the infused hemisphere.

In patients with superficial bladder cancer HAMLET instillations recently reduced tumor size and caused apoptosis-like death of tumor cells but the study was not designed to examine a therapeutic effect. Thus, we evaluated the therapeutic effects of HAMLET for bladder carcinoma in a murine bladder cancer model. Results suggest that HAMLET delays tumor growth and cell death mainly occurs in tumor tissue.

Monday, April 19, 2010

More on crashing in ash

My son, David, the Formula 1 engineer is stuck in China following the Grand Prix in Shanghai. Theoretically, he won't be home until May 2nd. Meantime, as I predicted yesterday, questions are being asked about the over reaction of the aviation authorities. From today's Telegraph:

Giovanni Bisignani, director-general, the International Air Transport Association, the airlines' trade body was scathing about the European response to the ash cloud.

"This is a European embarrassment and it's a European mess,” he told the BBC Radio 4 Today programme. It took five days to organise a conference call with the ministers of transport. Europeans are still using a system that's based on a theoretical model, instead of taking a decision based on facts and risk assessment. This decision (to close airspace) has to be based on facts and supported by risk assessment. We need to replace this blanket approach with a practical approach."

European air control authorities have admitted that they have interpreted international guidelines “more rigorously” than US.

“I do not think that Europe needs to be stricter than a country such as America, where you have a lot of volcanoes erupting. Those people have a lot of experience and do not close the whole airspace,” Camiel Eurlings, the Dutch transport minister, admitted. If remain on the present source, then I predict we remain in this misery for a very long time. That will not help travellers or the air sector and it is probably not necessary.”

On Sunday Willie Walsh, BA’s chief executive, joined four crew in a test flight from London to Cardiff. The flight, which took the aircraft out over the Atlantic Ocean, lasted two hours and 46 minutes with flying conditions described as “perfect”. Engineers at the airline are studying the effects of the flight on engines before concluding whether it is safe to fly or not. A BA spokesman said: “We would not be doing this if we did not think it was safe and didn’t have the necessary permission. We would not do anything which would jeopardise our crew or aircraft.”

Lufthansa also flew 10 aircraft from Munich to Frankfurt on Saturday with the blessing of the safety authorities. A spokesman said: “We found no damage to the engines, fuselage or cockpit windows. This is why we are urging the aviation authorities to run more test flights rather than relying on computer models.”

Ulrich Schulte-Strathaus, the Secretary General of the Association of European Airlines, said: “Verification flights undertaken by several of our airlines have revealed no irregularities at all; this confirms our requirement that other options should be deployed to determine genuine risk”.

For my son, this will all be a bit of an adventure, but we shouldn't be blind to the difficulties that the flight ban is causing. This from today's Times:

A British toddler was in a critical condition last night after bone marrow needed for a transplant was held back in Canada. She was one of 16 patients said to be in “critical need” because of the lack of bone marrow supplies.

The International Civil Aviation Authority said that the disruption was worse than that caused by the shutdown of air travel after 9/11. Airlines are reported to be losing at least $200 million (£130 million) a day.

Added later:

My son has a friend at BA who sold him his chocolate Labrador. She has managed to get him on a flight to Los Angeles and thence to London. He should be home at the weekend.

Sunday, April 18, 2010

The Hurt Locker

For my birthday I had a DVD of The Hurt Locker, Kathryn Bigelow's Oscar winning movie. I finally managed to watch it last night. I have a fine collection of War Films and although it is a good film in some respects with lots of bangs and flashes, it must have been a poor year if it swept the board at the Oscars.

It is about the men who defuse bombs. We know that they are heroes and far too many have returned home in body bags. It is a job I just could not do. Many years ago there was a television series, Danger UXB, starring Anthony Andrews (Brideshead Revisited) which covered the same ground. This film saved money by using stars like Guy Pearce, Evangeline Lily (Lost), David Morse (St Elsewhere's) and Ralph Fiennes for what looked like a day's filming, and the main parts were played by actors I had never noticed before.

As usual for modern films I had the subtitles switched on, though this just emphasized the profanity of the language. I suppose it it how soldiers speak, but not in my living room.

The hero was a man who was so reckless as to be in love with war - the same character that Steve McQueen plays (rather better) in the old film, "The War Lover". I think the film rather pulled its punches in that the only leading character to die was a wuss of an Army Psychiatrist, who was so naive it's a wonder that they let him travel without his nanny.

I doubt that the film will do much for American/Iraq relations. The Iraqis came over as nasty underhand cowards and the Americans as bombastic drunks. There was one extended passage where the bomb disposal squad go 'Haji hunting' at night. It illustrated the gung-ho nature of the film's hero, but it was extremely difficult to follow what was happening.

In summary just like they don't make Westerns like they used to, they don't may war films either.

Ash in the sky

Just how reliable are the warnings that flying is dangerous because of the black cloud from Iceland? I read this in today's Independent on Sunday:

"KLM, the Dutch subsidiary of Air France, says it has flown a plane through the cloud of volcanic ash covering Europe without suffering any damage. KLM carried out a test flight above Dutch air space yesterday. It says initial inspections afterward showed no damage or irregularities from the ash in the air that has led to a ban on air travel over much of Europe since Friday."

Bloggers have suggested that the ban might be an over-reaction from discredited meteorologists.

I picked up this from one of them:

"Today I made a flight over Europe with a twin engine plane, not a jet but a twin prop. Before take off I replaced the air filters and sprayed them with oil to be sure any particle would stick. I don’t tell you from which airport I departed but I flew over the eastern parts of the Netherlands, Belgium, Luxembourg, France, Germany, Switzerland, Austria, and Germany, no traffic, no worries. The flight levels were between 2500 and 18000 ft. I flew under VFR conditions during the entire flight without any problems.

When I returned I took out the air filters, put them in a plastic bag and send them to a friend of mine for analysis. Yes, I am sure I scooped up some particles but I have seen much worse with Sahara dust clogged filters in the past!"

However, a light plane crashed a few miles north of here at 5.20 pm yesterday and two people were killed. I hear from friends at church that the pilot was Richard Wheeler, a member at Christ Church Westbourne, returning from Spring Harvest. An unconfirmed rumor suggests that the passenger was a local surgeon, a member of the same church. There is only one report so far, picked up by the BBC and the Guardian and no more details are given. It was thought that the volcano had nothing to do with it, but we must wait for a report from Air Accident Investigators.

Added later: It is confirmed. The passenger in the plane was Shorland Hosking, a surgeon from Poole. He had once been a member of my church, and I knew him.

Wednesday, April 14, 2010

Enduring Hardship: 1 Peter 4:1-6

There has been a flurry of articles in the press about Christians suffering - not in Nigeria or Iraq, but in the UK.

There was the British Airways check-in girl who was banned from wearing a cross while Muslims were allowed hijabs and Sikhs allowed to wear ceremonial daggers. There was the couple with a bed and breakfast service in their own home who would not allow two men to share a bed. There was the nurse who was dismissed for offering to pray for her patients. There have been Christian Union Societies prevented from using University premises because non-Christians couldn't be members. They actually claimed that all religions don't lead to God and that it is only through Jesus that you can come to God.

As persecutions go, these are pretty small beer. Wearing a cross is not compulsory for a Christian and in any case one can be worn unobtrusively. No-one is forced to open up their house to guests and if you want to keep homosexuals out are you equally fervent about banning adulterers or mere fornicators? And no-one needs permission to pray for anyone. Just do it. The Christian Union case was overturned by a court - so no persecution there. What these instances show, though, is that the agenda of the secular world is different from that of the Christian one.

The world winks at sin, whether it be sex outside marriage, padding your CV with fictitious achievements, evading tax, lying to your spouse, illegally downloading music, 'professional fouls' at football matches, unkind gossip, abandoning one's parents, drawing benefits instead of working when work is available or simply speeding on the motorway. Christians not only recognize these as sinful, but set themselves higher standards, such as caring for widows and orphans, visiting those in need, whether from sickness or imprisonment, relieving poverty and sharing the gospel.

No wonder, when cultures clash, that Christians feel themselves to be persecuted. How should we cope?

Therefore, since Christ suffered in his body, arm yourselves also with the same attitude, because he who has suffered in his body is done with sin. As a result, he does not live the rest of his earthly life for evil human desires, but rather for the will of God. For you have spent enough time in the past doing what pagans choose to do—living in debauchery, lust, drunkenness, orgies, carousing and detestable idolatry. They think it strange that you do not plunge with them into the same flood of dissipation, and they heap abuse on you. But they will have to give account to him who is ready to judge the living and the dead. For this is the reason the gospel was preached even to those who are now dead, so that they might be judged according to men in regard to the body, but live according to God in regard to the spirit.

This passage from 1 Peter chapter 4 gives us the answer. We should expect tribulation because Christ himself tells us to expect it. We need to arm ourselves with the same attitude as Christ. What is this attitude?

The word 'attitude' refers to a way of thinking, but it has its origins in posture. It means to see things from a particular point of view. A man hanging from a tree sees things differently from one standing on the ground. He has a different viewpoint. Christ's attitude was to see things as a sojourner; one who is passing through. He had the experience of eternity past and eternity future. He saw things not just as a carpenter from Galilee but as the creator and sustainer of the Universe. He was not tied to the here and now.

Remember James Garner in "Support your local Gunfighter"? To the concerns of the locals who were worried about lawlessness and wanted to recruit him as sheriff, his constant refrain was "I'm leaving town tomorrow." That should be our attitude as well. This world is not our home, we're just a-passing through. To have the attitude of Christ we must see things from a wider perspective. St Paul wrote "I consider that our present sufferings are not worth comparing with the glory that will be revealed to us." (Romans 8:18) and "For our light and momentary troubles are achieving for us an eternal glory that far outweighs them all" (1 Corinthians 4:17)

As Christians we are not to seek suffering, but be assured, suffering will come. And when it comes, if we don't have the attitude of Christ, we won't survive it.

'To be done with sin' is to be holy. Earlier in his letter Peter talks about being refined by fire. "You may have had to suffer grief in all kinds of trials. These have come so that your faith may be proved genuine." Going through refining fire is not a pleasant experience. It's not like an operation for which you are anesthetized and then sedated with morphine until the pain is gone. Like the thorn in the flesh that Paul endured, the pain may be something that never goes: a lost son in Afghanistan, a husband who betrays you, terminal cancer, or a daughter lost to drugs. There is no way to gloss over such suffering, but facing it with the attitude of Christ will sustain you. There will be an end to suffering just as there will be an end to injustice. There will be a time when "he will wipe away all tears from your eyes".

What is it about the pleasures of this world that so ensnare us? Debauchery, lust, drunkenness, orgies, carousing... They are portrayed as young love, passion, having a good time, merry-making, free-love, partying... To our young people it seems so terribly attractive. We oldies are portrayed as spoilsports. The consequences are hidden: venereal disease, unplanned pregnancy, cancer, liver failure, drug overdose, road accidents, suicides, guilt, inability to build a relationship, poverty... the list is endless. It is only the Devil's 'sport' we wish to spoil.

The world stands amazed that we don't want to join in. As a physician I have seen so much unhappiness caused by wrong lifestyle choices. That's not to say that lives are irredeemable, but often, as brands saved from the burning, they end up rather singed.
Nevertheless, the world mocks us. God-botherers! Mamby-pambies! Pie in the sky when you die!

If I were certain that I didn't have to face a judge I might well become a vigilante. It is certain that there is no justice in this life. Crooks and liars live in the lap of luxury. Only about 5% of crime is solved. The police don't even bother to investigate burglaries. A child soon learns to cry, "It's not fair!" They are right to do so. It isn't. In this life don't expect fairness or justice.

So don't expect that your suffering will be relieved any time soon. It is the way of things. I was watching a TV program the other night about the history of Christianity. It featured a huge church in South Korea. The Yoido Full Gospel Church is a Pentecostal church on Yeouido Island in Seoul, South Korea. With about 830,000 members, it is the largest Christian congregation in South Korea, indeed, in the whole world. It was founded and has been led by David Yonggi Cho since 1958.

Pastor David Yonggi Cho preaches Three-Fold Blessing (the blessing of the spirit, soul, and body), proclaiming that physical health and financial prosperity are as much a part of God's will for Christians as the salvation of the soul. Now it is certainly true that God does not bless those who 'walk in the counsel of the ungodly', but who is going to accuse those murdered at Jos or those persecuted by Nero, or Latimer and Ridley of living ungodly lives. Suffering does not correlate with personal sin. Rather, as the book of Hebrews tells us, God is treating us like sons. No discipline seems pleasant at the time, but painful. Later on, however, it produces a harvest of righteousness and peace.

The hymns sung at the Korean church on television included 'Blessed Assurance' and 'I know whom I have believed', two of the songs I should like sung at my own funeral. Here is another one from Stuart Townend:

There is a hope that burns within my heart,
That gives me strength for ev'ry passing day;
a glimpse of glory now revealed in meager part,
Yet drives all doubt away:
I stand in Christ, with sins forgiv'n;
and Christ in me, the hope of heav'n!
My highest calling and my deepest joy,
to make His will my home.

There is a hope that lifts my weary head,
A consolation strong against despair,
That when the world has plunged me in its deepest pit,
I find the Savior there!
Through present sufferings, future's fear,
He whispers, "Courage!" in my ear.
For I am safe in everlasting arms,
And they will lead me home.

There is a hope that stands the test of time,
That lifts my eyes beyond the beckoning grave,
To see the matchless beauty of a day divine
When I behold His face!
When sufferings cease and sorrows die,
and every longing satisfied,
then joy unspeakable will flood my soul,
For I am truly home.

General Elelction

We have an election going on. What to I wish for?

Small government. The present lot are altogether too intrusive. Their first responsibilty is to protect citizens from outside attack. Not doing too well on that. The second is to create sound money. Not a high score there, either. The third is the rule of law. I rest my case.

Local involvement. I am sick of being told what to do by Brussels or Edinburgh or even London. I came to Bournemouth for its pleasant parks, mild climate, selective education and superlative hospitals. Leave us alone!

Personal responsibility. Cradle-to-grave nurturing by a nanny-state breeds weakness, dependency and inertia. We need to take responsibility for the behavior and education of our children, for the tidiness of our town, for the quality of our hospitals and the state of our roads. Are we to suppose that Brussels cares about potholes in Holdenhurst Road or whether the 9.53 gets into London on time, or whether ASDA sells minced beef in half pound packs? They apparently care about how straight bananas are or whether we use ounces or grammes.

Is there any party I should support?

Tuesday, April 13, 2010

Old age

The world is getting older. A while ago there was a huge expansion of young people in third world countries. AIDS and contraception are curtailing that. In 1984 Japan had the youngest population in the developed world; by 2005 it had become the world's most elderly country. Soon it will become the first country where most people are over 50 years old. Japanese men can expect to reach 79 and women 86. But it it not just that the old aren't dying, it's also that the Japanese have practically given up having babies. The fertility rate is just 1.2 children per woman; A ratio of 2.1 is needed to maintain a steady population.

But it's not just Japan. The longevity revolution affects every country, every community and almost every household. Change is coming that will effect the economy, the family, politics and the world order.

This is frightening, especially for rich nations. In Germany, France and Japan, there are fewer than two taxpaying workers to support each retired pensioner. In Italy, the figure is already fewer than 1.3.

However, there might be a bright side. It isn't only pop singers like Mick Jagger and Tina Turner (who took to the stage in London, dancing in heels and a microskirt in her 70th year) who behave in their dotage like they did as teenagers. Last year we had the elderly Tom Watson leading in the Open and now Fred Couples a first round leader in the Masters. And millions of ordinary middle-class retired people continue working at everything from lucrative consultancies to teaching literacy or English as a foreign language. They are often more valuable than the young workers that the experts imagine are supporting them: in fact, the growing number of society's most qualified, most experienced individuals is a huge demographic dividend.

The idea of a retirement age was invented by Otto von Bismarck in the 1880s. When as chancellor of Germany he needed a starting age for paying war pensions, he chose the age of 65 because that was the age when ex-soldiers typically died. Today, women can expect nearly 30 years of retirement, and men 20 years.

Last night I watched an episode of the Swedish TV detective, Wallender. At 62 he is horrified that he will shortly have to retire. What's a man supposed to do? Plant potatoes and wait for the grim reaper?

A national do-it-yourself store has taken a lead by employing older men who are able to give advice about how to do jobs around the house. I know of doctors in their eighties leading teams in American hospitals. Indeed, some of my American colleagues were astonished that I had retired so early.

Some older people do need healthcare, but many others are fit, competent and self-sustaining. Across Europe, typically only one retired person in 20 lives in a care home. In the UK, of 10 million over-65s, just 300,000 (or 3%) live in care homes. What is to become of our older citizens?

Have you watched day-time TV? Recycled episodes of Poirot and Midsummer Murders, a grey haired Dick Van Dyke, children's cartoons, Escape to the country, Cash in the Attic, Antiques Road Show, Oprah, Rikki Lake, Judge Judy, Ugh! There has to be more in life.

To my mind, ageism in employment must stop. At 60 you can't do what you could at 40 and at 80 you're no longer 60. You do get tired. But mixing with people keeps you young. It's not that you need the money. Many people find the mortgage paid, children catered for, the pension sufficient. Your local hospital can't afford to employ a receptionist? Most volunteers could easily do the job. You may not be up to an 8 hour shift, but you could easily manage 2 or 3.

Many could do more. I find a couple of hours a week teaching the Fellows to be rewarding. In fact, I would happily do a clinic (unpaid) once a week as long as I could abstain from medical politics.

The elderly are an underused resource.

Saturday, April 10, 2010

Drug resistance

This paper has just appeared in Cell.

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
Sreenath V. Sharma et al Cell 2010 DOI 10.1016/j.cell.2010.02.027

Accumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly ‘‘drug-tolerant’’ cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells
transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.

In other words some cancer cells can only become resistant to anti-cancer agents by using a little-used pathway to keep alive. Block that pathway and they die. Some evidence that drug resistance in cancer cells may be reversible.

Wednesday, April 07, 2010

Foot in the mouth club

Michelle Obama tells of the time when she and Barack visited his home country of Kenya (she pronounces it Kinya, but I guess that was she what she meant) (unless there is a Kinya province in Hawaii that I haven't heard about)

Tuesday, April 06, 2010

What is CAL 101?

The hematological world was entranced when in 1999 imatanib (Gleevec in America, Glivec in the rest of the world; pronounced the same however it is spelled) was shown in a phase 1 dose finding study to introduce molecular remissions in chronic myeloid leukemia. Imatanib is an orally active tyrosine kinase inhibitor. There are about 1800 different kinases in the human cell, and the hunt was on for other inhibitors that would work in other forms of cancer.

So far the kinase inhibitors that have been tested have not been as good as Glivec - no, that's not true, there are better inhibitors than Glivec, there hasn't been such a good target as bcr/abl in other cancers.

CAL 101 is a small molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA phosphoinositide-3 kinases (PI3K) with potential immunomodulating and antineoplastic activities. It inhibits the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), preventing the activation of the PI3K signaling pathway.

This pathway is illustrated to the left of this schematic diagram, which shows some of the ways that a stimulus to the surface of a cell is transmitted to the nucleus where transcription factors are activated. Trancription factors are responsible for the reading of DNA and the subsequent enactment of its message in the cell. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic lineages. Thus it could be seen as targeted towards leukemias and lymphomas, though it would also suggest that suppression of normal hematopoiesis might be a side effect.

An interim report of a phase 1 clinical trial of CAL-101 in patients with relapsed or refractory CLL, indolent non-Hodgkin’s lymphoma (NHL), aggressive NHL, acute myeloid leukemia (AML), and multiple myeloma (MM) was given at last year's IWCLL meeting in Barcelona. At this interim assessment, 29 percent of CLL patients treated at the dose level at which it was decided to expand the cohort had partial responses observed after 28 days of therapy (1 cycle) and 94 percent achieved evidence of biologic activity with a greater than 50 percent shrinkage of lymph node tumors. Five out of six partial responders continue treatment with CAL-101, with the longest response greater than 224 days. All patients had prior rituximab and fludarabine therapy and nearly half of the patients had prior alemtuzamab therapy. Half of the patients were refractory to their last therapy prior to entering the study. A low incidence of hematologic toxicity was observed. The dose limiting toxicity in the study was an elevation of transaminases (ALT and AST), which has been both monitorable and reversible and patients were usually able to resume therapy at a lower dose.

Last month a new trial with Ian Flinn as Principle investigator was begun in CLL. This will be a Phase I Study to Investigate the Safety and Clinical Activity of CAL-101 in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia. The Primary Outcome Measures will be Safety of CAL-101 in combination with rituximab and bendamustine - assessed by adverse events, vital signs, clinical laboratory tests and ECG. The Secondary Outcome Measures will be clinical activity evaluated by clinical response rate - assessed by CT scan, clinical laboratory tests and bone marrow biopsy if indicated; plasma concentrations of CAL-101; plasma concentrations of bendamustine in a select subset of patients; and the pharmacodynamic effects of CAL-101 treatment - assessed by comparing pre and post dose blood samples.

There will be three arms to the study: CAL-101 daily for 12 28-day cycles plus treatment with rituximab for 8 weekly doses over the first 2 cycles (CAL-101 100 mg by mouth twice daily; Rituximab 375 mg/m2 administered intravenously); CAL-101 daily for 12 28-day cycles plus bendamustine on days 1 & 2 of Cycles 1-6 (CAL-101 100 mg by mouth twice daily; Bendamustine 90 mg/m2 administered intravenously); and CAL-101 daily for 12 28-day cycles plus rituximab on day 1 and bendamustine on days 1 & 2 of Cycles 1-6 (CAL-101 100 mg by mouth twice daily; Rituximab 375 mg/m2 administered intravenously; Bendamustine 90 mg/m2 administered intravenously). Inclusion criteria are patients with CLL or indolent lymphoma, previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 month of the last course of a standard regimen)
and WHO performance status of ≤ 2. Exclusion criteria: Not a good candidate according to the clinical judgment of the investigator; Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over-expression; Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests; Had treatment with a short course of corticosteroids for symptom relief within 1-week prior to the baseline tests; Has had an allogeneic hematopoietic stem cell transplant; Has known active central nervous system involvement of the malignancy; Is pregnant or nursing; Has active, serious infection requiring systemic therapy; Has a positive test for human immunodeficiency virus (HIV) antibodies; Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.

Four centers are registered: Nashvill, NCI, Cornell and St Louis. Details can be found here.

This may not be Glivec but it looks a worthwhile and encouraging agent acting in a way different to anything else that has been tried in CLL.

Monday, April 05, 2010

You can't handle the truth!

"You can't handle the truth!" So screamed Col. Nathan R. Jessep (played by Jack Nicholson) in the Rob Reiner film "A Few Good Men." He then launches into a tirade against Lieutenant Kafee (played by Tom Cruise)

"Son, we live in a world that has walls and those walls have to be guarded by men with guns. Whose gonna do it? You? You, Lt. Weinburg? I have a greater responsibility than you could possibly fathom. You weep for Santiago and you curse the marines. You have that luxury. You have the luxury of not knowing what I know. That Santiago's death, while tragic, probably saved lives. And my existence, while grotesque and incomprehensible to you, saves lives. You don't want the truth because, deep down in places you don't talk about at parties, you want me on that wall; you need me on that wall. We use words like honor, code, loyalty. We use these words as the backbone of a life spent defending something. You use them as a punchline. I have neither the time nor the inclination to explain myself to a man who rises and sleeps under the blanket of the very freedom that I provide and then questions the manner in which I provide it. I would rather you just said thank you and went on your way. Otherwise, I suggest you pick up a weapon, and stand a post. Either way, I don't give a damn what you think you are entitled to."

Jessep has a different system of priorities to Kafee; a different version of the truth. One of the discoveries of the post-modernists is that truth is relative. Perhaps they overemphasize this aspect, but it is an insight of some validity. Many witnesses may view a car crash from a different direction and each see something or at least emphasize something that the others have missed. But the bottom line is that the car has crashed. In the Hitchcock film, "The Birds" a dropped cigarette sparks a major explosion at a gas station. We know that the real problem is that the birds have gone haywire, but someone, concentrating on that detail, might use the scene as a case against smoking, or even against fossil fuels.

One of our problems is that we never see the complete picture. Scientists tell us that even by observing an event, we influence it. Sometimes I fantasize, when my soccer team loses and I was not there to observe it, that had I been there I might have made a difference. Perhaps a smart remark would have been taken up by the crowd. It might have raised the mood, which could have inspired the team to greater effort so that another goal would have been scored and the match saved. Fantasy, indeed, but might it not be true?

When Pilate asked, "What is Truth?" he was being a cynic. He'd seen so much that he did not believe in absolute truth. Modern man might say, "It may be true for you, but it's not true for me." as if there were a multitude of truths. Yet the car still crashed, the gas station exploded, Santiago was murdered. However, we 'see' the sequence of events we cannot uncrash the car, unexplode the gas station, bring Santiago back to life.

When I was a young doctor I worked for a surgeon who used to counsel his cancer patients thus, "My dear, you have a small growth, but you mustn't worry. I am going to cut it out and cure you." The word 'cancer' was never mentioned. It was referred to as a 'neoplasm' or a 'mitotic lesion'. It was terribly paternalistic and resulted in surgeons being regarded as gods. Things are very different now. It is expected that patients should be given every detail of their diagnosis (except in Japan where cancer is still never mentioned).

I wonder if this is a good thing. Truth about the future is nearly always contingent truth. If this happens then that will happen. It is also frequently speculative truth with a varying degree of uncertainty. Given what we know, this is likely to happen, but there is a one in ... 10, 100, 1000, ... chance that it won't.

Moreover, patients don't hear what is said. The mention of the word 'cancer' still screens out x number of subsequent sentences. Patients asked to recall what was said to them after the word cancer, usually give a garbled version of the subsequent conversation. It was my practice when breaking bad news to send the patient to an experienced senior nurse who had sat in on the conversation, so that she could rehearse what had been communicated to the patient.

I have heard patients complain, "Why won't the doctors tell me what is wrong with me?" when I know for certain that they have been told several times. I can only conclude, that they haven't been told what they wanted to hear.

I have been through this experience from the other side of the desk. I have become adroit at putting both the best and the worst face on the news that I receive. I am well capable of thinking up the most dismal prognosis for myself following a twinge in my tummy, yet at the same time of thinking up a totally benign explanation for the most worrying of X-ray findings. I shouldn't think that I am very different from most patients - I may have more information, but I am subject to the same emotions.

"You can't handle the truth!" No I can't. But then I don't know what the truth is.

When I tell a patient that his immunoglobulin genes are unmutated I can add that the median survival for such patients is 8 years. But that still means that 50% of patients that I studied lived longer than 8 years. I could tell him that the longest survivor that I saw lived for 12 years, but my study didn't look at huge numbers of such patients, there may well be many others who have survived for longer that I didn't see. And the patients I saw date from the early nineties and treatments have moved on from there. In any case in eight years time CLL might be a totally curable disease.

One thing I am sure about. All of us are going to die, unless the Lord returns first, whether we are nine or ninety. Should we metamorphose into Methuselah - he died aged 969, drowned it is said in the Universal Flood - our end is nigh.

But of this I am also certain. Jesus Christ died to save sinners and rose from the dead to demonstrate that the sacrifice was sufficient. He ascended into heaven and sits at the right hand of God the Father and one day He will return to judge the living and the dead. The only escape from judgement is to put your trust in Him who saves to the uttermost.

Francis Schaeffer called that 'True Truth'.

Sir Alec Bedser R.I.P.

Alec Bedser has died at the age of 91. He has a claim to be the greatest swing bowler of all time. He and his identical twin brother, Eric, had their cricketing careers abbreviated by the war in which they served in the RAF. but in 1946 after playing only 7 County matches for Surrey, he was selected to play for England against India. In two test matched he took 22 wickets.

He played in 51 test matches, taking 236 wickets at an average of 22.9. His best season was 1953 when he took 39 Australian wickets at an average 17.48. England beat (a Bradman-less) Australia for the first time since the 1932-3 'Bodyline' tour. Bedser was the master of the leg-cutter, a ball that started outside the off stump, swung in the air to the leg and then cut back after hitting the pitch to take the off stump. Even Bradman had no answer to it.

After his retirement he and his brother set up an office stationary company that was later assimilated into Rymans. It left them fairly well off. They had started life more humbly in Reading, the sons of a bricklayer. They lived first in two rooms belonging to an aunt on Horsell Common, and then at Knaphill. They were the third generation of the family to live in the Woking area. Very far from spoilt, the twins grew up with a cautious attitude to life which allowed no scope for frills or frivolity. From the age of five they walked a mile each way to Maybury Junior School. Later, at Monument Hill Central School, they impressed with their industry.

At 14, they began work as clerks in a solicitor’s office in Lincoln’s Inn Fields, which left them with little spare time; even on Saturdays they were not free until 1.30pm. Alan Peach, a former Surrey all-rounder, opened a cricket school at Woking. The twins devoted every moment to the school, learning their trade with long stints of bowling. Peach recommended the Bedsers to the Oval, and in April 1938 they abandoned the law to join the Surrey ground staff. In the summer their wages were £2 a week plus minimal match fees; in the winter they were paid £1 per week as a retainer. There was a rigid hierarchy: young players were not allowed to start a conversation with, or even to enter the dressing room of senior professionals.

It was a sterner age and it rubbed off on Alec Bedser. Later, when he became Chairman of the England selectors he dropped the master batsman, Tom Graveney, for daring to play in a Charity Match on the Sunday that was the rest day in the middle of a test match. Graveney never played for England again until Bedser retired as Chairman. His time as chairman was marred by their failure to select Basil d'Olivera for the MCC against South Africa after receiving threats from the South Africans that a 'colored' player would not be welcome. He somewhat redeemed his position by choosing d'Olivera as a replacement when Tom Cartwright withdrew injured. Prime Minister Vorster, thereupon cancelled the tour.

Alec Bedser was appointed OBE in 1964, CBE in 1982, and in 1997 became the only England bowler ever to be knighted. He was President of Surrey County Cricket Club in 1987-88.
Eric died in 2006. Neither of the Bedser twins married.

Friday, April 02, 2010

Obama snubs

Most people in the United Kingdom of Great Britain and Northern Ireland have tended to side with America on most things. I wonder for how much longer? With the Canadians they have borne the brunt of the fighting in Afghanistan and they were the major supporter in Iraq, despite the growing unpopularity of the war there. Going back as far as Korea, the British were the major supporters of America's war there, and suffered some of the severest losses. Mrs Thatcher was very close to Ronald Reagan, and can claim a share in ending the Cold War.

But recently, this new President in America seems to be going out of his way to be offensive. The first thing he did when obtaining office was to return a bust of Winston Churchill that the British government had loaned the White House after 9/11. He then presented Gordon Brown with a set of DVDs that wouldn't work on British machines - it was almost as though he realized late that an exchange of gifts was usual, so he sent his kids round to the nearest corner shop for a present.

Then when Brown was in town the only time he could fit him in for a meeting was as he walked through the United Nation's kitchens.

For all America claims to believe in self-determination, this Administration would rather curry favor with the Argentinians than accept the near-unanimous vote of the Falkland Islanders to remain British.

Some people see this as a hangover from the attitudes of his biological father who had definite anti-British feelings as a Kenyan national at the time of the Mau-Mau uprising, others will concur with Mr Obama's senior aides who told a recent campaign biographer that they found meeting Mr Brown a 'depressing experience' and said there was an 'end of regime feel' to his Government, but I think that this is just symptomatic of the whole left wing Administration, that doesn't know who its friends are. Recently we have seen snubs for Indonesia and Australia and a mega-insult to Israel, while he actually bows to the King of Saudi Arabia.

Or perhaps America has just elected a very rude man to be their President. I Googled "Obama snubs" and got 213,000 hits.